Citations

The American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO‐HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Bell's Palsy. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 11 recommendations developed encourage accurate and efficient diagnosis and treatment and, when applicable, facilitate patient follow‐up to address the management of long‐term sequelae or evaluation of new or worsening symptoms not indicative of Bell's palsy. There are myriad treatment options for Bell's palsy; some controversy exists regarding the effectiveness of several of these options, and there are consequent variations in care. In addition, there are numerous diagnostic tests available that are used in the evaluation of patients with Bell's palsy. Many of these tests are of questionable benefit in Bell's palsy. Furthermore, while patients with Bell's palsy enter the health care system with facial paresis/paralysis as a primary complaint, not all patients with facial paresis/paralysis have Bell's palsy. It is a concern that patients with alternative underlying etiologies may be misdiagnosed or have an unnecessary delay in diagnosis. All of these quality concerns provide an important opportunity for improvement in the diagnosis and management of patients with Bell's palsy.

Objective Bell's palsy, named after the Scottish anatomist, Sir Charles Bell, is the most common acute mono‐neuropathy, or disorder affecting a single nerve, and is the most common diagnosis associated with facial nerve weakness/paralysis. Bell's palsy is a rapid unilateral facial nerve paresis (weakness) or paralysis (complete loss of movement) of unknown cause. The condition leads to the partial or complete inability to voluntarily move facial muscles on the affected side of the face. Although typically self‐limited, the facial paresis/paralysis that occurs in Bell's palsy may cause significant temporary oral incompetence and an inability to close the eyelid, leading to potential eye injury. Additional long‐term poor outcomes do occur and can be devastating to the patient. Treatments are generally designed to improve facial function and facilitate recovery. There are myriad treatment options for Bell's palsy, and some controversy exists regarding the effectiveness of several of these options, and there are consequent variations in care. In addition, numerous diagnostic tests available are used in the evaluation of patients with Bell's palsy. Many of these tests are of questionable benefit in Bell's palsy. Furthermore, while patients with Bell's palsy enter the health care system with facial paresis/paralysis as a primary complaint, not all patients with facial paresis/paralysis have Bell's palsy. It is a concern that patients with alternative underlying etiologies may be misdiagnosed or have unnecessary delay in diagnosis. All of these quality concerns provide an important opportunity for improvement in the diagnosis and management of patients with Bell's palsy. Purpose The primary purpose of this guideline is to improve the accuracy of diagnosis for Bell's palsy, to improve the quality of care and outcomes for patients with Bell's palsy, and to decrease harmful variations in the evaluation and management of Bell's palsy. This guideline addresses these needs by encouraging accurate and efficient diagnosis and treatment and, when applicable, facilitating patient follow‐up to address the management of long‐term sequelae or evaluation of new or worsening symptoms not indicative of Bell's palsy. The guideline is intended for all clinicians in any setting who are likely to diagnose and manage patients with Bell's palsy. The target population is inclusive of both adults and children presenting with Bell's palsy. Action Statements The development group made a strong recommendation that (a) clinicians should assess the patient using history and physical examination to exclude identifiable causes of facial paresis or paralysis in patients presenting with acute‐onset unilateral facial paresis or paralysis, (b) clinicians should prescribe oral steroids within 72 hours of symptom onset for Bell's palsy patients 16 years and older, (c) clinicians should not prescribe oral antiviral therapy alone for patients with new‐onset Bell's palsy, and (d) clinicians should implement eye protection for Bell's palsy patients with impaired eye closure. The panel made recommendations that (a) clinicians should not obtain routine laboratory testing in patients with new‐onset Bell's palsy, (b) clinicians should not routinely perform diagnostic imaging for patients with new‐onset Bell's palsy, (c) clinicians should not perform electrodiagnostic testing in Bell's palsy patients with incomplete facial paralysis, and (d) clinicians should reassess or refer to a facial nerve specialist those Bell's palsy patients with (1) new or worsening neurologic findings at any point, (2) ocular symptoms developing at any point, or (3) incomplete facial recovery 3 months after initial symptom onset. The development group provided the following options : (a) clinicians may offer oral antiviral therapy in addition to oral steroids within 72 hours of symptom onset for patients with Bell's palsy, and (b) clinicians may offer electrodiagnostic testing to Bell's palsy patients with complete facial paralysis. The development group offered the following no recommendations : (a) no recommendation can be made regarding surgical decompression for patients with Bell's palsy, (b) no recommendation can be made regarding the effect of acupuncture in patients with Bell's palsy, and (c) no recommendation can be made regarding the effect of physical therapy in patients with Bell's palsy.

Loss of sensation and increased sensory phenomena are major expressions of varieties of diabetic polyneuropathies needing improved assessments for clinical and research purposes. We provide a neurobiological explanation for the apparent paradox between decreased sensation and increased sensory phenomena. Strongly endorsed is the use of the 10-g monofilaments for screening of feet to detect sensation loss, with the goal of improving diabetic management and prevention of foot ulcers and neurogenic arthropathy. We describe improved methods to assess for the kind, severity, and distribution of both large- and small-fiber sensory loss and which approaches and techniques may be useful for conducting therapeutic trials. The abnormality of attributes of nerve conduction may be used to validate the dysfunction of large sensory fibers. The abnormality of epidermal nerve fibers/1 mm may be used as a surrogate measure of small-fiber sensory loss but appear not to correlate closely with severity of pain. Increased sensory phenomena are recognized by the characteristic words patients use to describe them and by the severity and persistence of these symptoms. Tests of tactile and thermal hyperalgesia are additional markers of neural hyperactivity that are useful for diagnosis and disease management.

Hepatocyte apoptosis is a hallmark of nonalcoholic steatohepatitis. We have previously observed that the saturated free fatty acids (FFAs) induce hepatocyte apoptosis in part via a death receptor 5 (DR5)-mediated signaling pathway. Cellular inhibitor of apoptosis protein 1 and 2 (cIAP-1 and cIAP-2) proteins are potent inhibitors of death receptor-mediated apoptosis. However, the role of the cIAPs in FFA-mediated hepatocyte apoptosis is unexplored. Our aim was to determine whether cIAPs are dysregulated during hepatocyte lipoapoptosis. cIAP proteins underwent rapid cellular elimination following treatment with the saturated FFAs palmitate (PA) and stearate. In contrast, PA did not decrease cIAP-1 and cIAP-2 mRNA expression in the cells. Degradation of cIAPs was dependent on their E3-ligase activity, suggesting that cIAPs undergo autoubiquitination that leads to proteasomal degradation. Huh-7 cells stably expressing shRNA targeting cIAP-1, but not cIAP-2, displayed enhanced sensitivity to PA-mediated apoptosis. Incubation with the SMAC mimetic JP1584, which induces rapid degradation of cIAPs, also enhanced PA-mediated apoptosis. Hepatocytes isolated from DR5 knockout mice exhibited reduced apoptosis following treatment with PA plus JP1584, implying that degradation of cIAPs sensitizes to DR5-mediated cell death pathways. A decrease of cIAP-1 was also observed in tissue from patients with nonalcoholic steatohepatitis compared with normal obese subjects. Collectively, these results implicate proteasomal degradation of cIAPs by FFA as a mechanism contributing to hepatocyte lipoapoptosis.

AbstractProstate cancer is the most common non‐cutaneous malignancy among men in the Western world, and continues to be a major health problem. Imaging has recently become more important in the clinical management of prostate cancer patients, including diagnosis, staging, choice of optimal treatment strategy, treatment follow up and restaging. Positron emission tomography, a functional and molecular imaging technique, has opened a new field in clinical oncological imaging. The most common positron emission tomography radiotracer, 18F‐fluorodeoxyglucose, has been limited in imaging of prostate cancer. Recently, however, other positron emission tomography tracers, such as 11C‐acetate and 11C‐ or 18F‐choline, have shown promising results. In the present review article, we overview the potential and current use of positron emission tomography or positron emission tomography/computed tomography imaging employing the four most commonly used positron emission tomography radiotracers, 18F‐fluorodeoxyglucose, 11C‐acetate and 11C‐ or 18F‐choline, for imaging evaluation of prostate cancer.

Summary Aging is associated with the development of insulin resistance, increased adiposity, and accumulation of ectopic lipid deposits in tissues and organs. Starting in mid‐life there is a progressive decline in lean muscle mass associated with the preferential loss of glycolytic, fast‐twitch myofibers. However, it is not known to what extent muscle loss and metabolic dysfunction are causally related or whether they are independent epiphenomena of the aging process. Here, we utilized a skeletal‐muscle‐specific, conditional transgenic mouse expressing a constitutively active form of A kt1 to examine the consequences of glycolytic, fast‐twitch muscle growth in young vs. middle‐aged animals fed standard low‐fat chow diets. Activation of the A kt1 transgene led to selective skeletal muscle hypertrophy, reversing the loss of lean muscle mass observed upon aging. The A kt1‐mediated increase in muscle mass led to reductions in fat mass and hepatic steatosis in older animals, and corrected age‐associated impairments in glucose metabolism. These results indicate that the loss of lean muscle mass is a significant contributor to the development of age‐related metabolic dysfunction and that interventions that preserve or restore fast/glycolytic muscle may delay the onset of metabolic disease.

Background HIV infection leads to activation of coagulation, which may increase the risk for atherosclerosis and venous thromboembolic disease. We hypothesized that HIV replication increases coagulation potentially through alterations in extrinsic pathway factors. Methods and Results Extrinsic pathway factors were measured among a subset of HIV participants from the Strategies for Management of Anti‐Retroviral Therapy ( SMART ) trial. Thrombin generation was estimated using validated computational modeling based on factor composition. We characterized the effect of antiretroviral therapy ( ART ) treatment versus the untreated state ( HIV replication) via 3 separate analyses: (1) a cross‐sectional comparison of those on and off ART (n=717); (2) a randomized comparison of deferring versus starting ART (n=217); and (3) a randomized comparison of stopping versus continuing ART (n=500). Compared with viral suppression, HIV replication consistently showed short‐term increases in some procoagulants (eg, 15% to 23% higher FVIII ; P <0.001) and decreases in key anticoagulants (eg, 5% to 9% lower antithrombin [ AT ] and 6% to 10% lower protein C; P <0.01). The net effect of HIV replication was to increase coagulation potential (eg, 24% to 48% greater thrombin generation from computational models; P <0.01 for all). The pattern of changes from HIV replication was reversed with ART treatment and consistent across all 3 independent comparisons. Conclusions HIV replication leads to complex changes in extrinsic pathway factors, with the net effect of increasing coagulation potential to a degree that may be clinically relevant. The key influence of changes in FVIII and AT suggests that HIV ‐related coagulation abnormalities may involve changes in hepatocyte function in the context of systemic inflammation. Clinical Trial Registration URL: ClinicalTrials.gov . Unique identifier: NCT 00027352.